Ziprasidone hydrochloride, namely 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride, of formula

is used as an antipsychotic. Its preparation is known from U.S. Pat. No. 4,831,031. Ziprasidone base and its pharmaceutically acceptable salts are pink in color, in fact Merck Index Online® reports that anhydrous ziprasidone hydrochloride is a “white to slightly pink powder”. The pink coloration, most likely due to highly coloring impurities, is present even in highly pure ziprasidone, for instance with purity above 99.9%. The pink coloration of the powders is a severe problem in the pharmaceutical chemistry, in that the APIs (Active Pharmaceutical Ingredients) should be free from coloring impurities to satisfy regulatory requirements. To date, efforts to remove said coloring impurities using, for example, adsorption on charcoal, have been dissatisfying. There is therefore the need for ziprasidone free from any coloring impurities.
Ziprasidone hydrochloride shows high permeability through biological membranes, which is favourable in terms of bioavailability. EP 965 343 reports that ziprasidone hydrochloride is sparingly water-soluble and, when obtained in the form of particles having diameter lower than or equal to 85, μm at least 70% of the compound dissolves within 45 minutes in aqueous solutions at physiological pH, independently of the particle size. Anhydrous ziprasidone hydrochloride is highly hygroscopic, in fact when exposed to air it spontaneously converts to the hydrate form. Particles of anhydrous ziprasidone hydrochloride with diameter lower than or equal to 85 μm still maintain high hygroscopicity, which affects work up, transportation, storage and formulation of pharmaceutical forms. There is therefore the need for anhydrous ziprasidone hydrochloride in form of particles having improved resistance to absorption of atmospheric humidity.